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The salutary action of melatonin and betaine, given singly or concomitantly, on cisplatin-induced nephrotoxicity in mice

Published on Thursday, 16 February 2023

Abstract

Cisplatin (CP) is commonly used in the treatment of various solid tumors. Its use, however, is hampered by nephrotoxicity.

In this study, we compared the effect of betaine and melatonin given singly, with that of a combination of these two agents on CP-induced nephrotoxicity in mice. CP (20 mg/kg, given intraperitoneally on the 8th day of 12 days of the experiment) showed the typical physiological, biochemical, and histologic features of nephrotoxicity. CP-treated mice showed a significant reduction in food intake, body weight, and urine and fecal output. It also induced significant increases in the plasma concentrations of urea, creatinine, uric acid, phosphorous, adiponectin, interleukin-1β, interleukin-6, transforming growth factor -β1, tumor necrosis factor-α, and cystatin C.

All these effects were significantly reduced by daily administration of betaine or melatonin at oral doses of 200 mg/kg and 10 mg/kg, respectively.

Furthermore, using the two agents in combination caused further significant reductions in the above parameters.

These findings suggest that betaine and melatonin concomitant use is likely to provide greater protection against CP-induced nephrotoxicity than when they are given singly, rendering them potentially suitable and safe agents to use in clinical trials to assess their possible beneficial actions in cancer patients receiving CP.

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- The Di Bella Method (A Fixed Part - Melatonin tablets. From 30-40mg/day up to 200mg/day orally in patients with advanced stage of cancer disease and/or patients without respond to traditional treatments);

- Melatonin use in cancer patients have started in 1974, when melatonin prepared according to Prof. Di Bella’s formulation [...]. For 11 days was administered to the patient, admitted to the general medical ward at the Maggiore-Pizzardi Hospital in Bologna, very slowly (over approx. 8 hours) and intravenously administered 1000 mg of melatonin for 11 days. During the course of each day, the patient was intravenously administered 4 saline drips of 500 ml, each containing ten 25 mg bottles of freeze-dried melatonin, lasting 2 hours, totaling 1000 mg per day. No other drug of any kind was administered in order to ascertain the effect of the MLT without interference [...]. From Melatonin with adenosine solubilized in water and stabilized with glycine for oncological treatment - technical preparation, effectivity and clinical findings;

- About Melatonin - In vitro, review and in vivo publications;

- Publication: Melmethoatonin anticancer effects: Review (from Di Bella's Foundation);

- Publication: Key aspects of melatonin physiology: 30 years of research (from Di Bella's Foundation);

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- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Fixed Part - Calcium, 2 grams per day, orally);

- The Di Bella Method (A Variable Part - Chondroitin sulfate, up to 3-4 grams per day, orally);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);